A Snapshot of Early Transcriptional Changes Accompanying the Pro-Neural Phenotype Switch by NGN2, ASCL1, SOX2, and MSI1 in Human Fibroblasts: An RNA-Seq Study.

Direct pro-neural reprogramming is a conversion of differentiated somatic cells to neural cells without an intermediate pluripotency stage. It is usually achieved via ectopic expression (EE) of certain transcription factors (TFs) or other reprogramming factors (RFs). Determining the transcriptional changes (TCs) caused by particular RFs in a given cell line enables an informed approach to reprogramming initiation.

Ally or traitor: the dual role of p62 in caspase-2 regulation.

Caspase-2 is a unique and conserved cysteine protease that is involved in several cellular processes, including different forms of cell death, maintenance of genomic stability, and the response to reactive oxygen species. Despite advances in caspase-2 research in recent years, the mechanisms underlying its activation remain largely unclear. Although caspase-2 is activated in the PIDDosome complex, its processing could occur even in the absence of PIDD1 and/or RAIDD, suggesting the existence of an alternative platform for caspase-2 activation.

Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the Yeast and a Glioblastoma Cell Line.

Proteasome inhibitors are used in the therapy of several cancers, and clinical trials are underway for their use in the treatment of glioblastoma (GBM). However, GBM becomes resistant to chemotherapy relatively rapidly. Recently, the overexpression of ribonucleotide reductase (RNR) genes was found to mediate therapy resistance in GBM.

Recombinant Strains of Oncolytic Vaccinia Virus for Cancer Immunotherapy.

Cancer virotherapy is an alternative therapeutic approach based on the viruses that selectively infect and kill tumor cells. Vaccinia virus (VV) is a member of the Poxviridae, a family of enveloped viruses with a large linear double-stranded DNA genome. The proven safety of the VV strains as well as considerable transgene capacity of the viral genome, make VV an excellent platform for creating recombinant oncolytic viruses for cancer therapy.

Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response.

We developed recombinant variants of oncolytic vaccinia virus LIVP strain expressing interleukin-15 (IL-15) or its receptor subunit alpha (IL-15Rα) to stimulate IL-15-dependent immune cells. We evaluated their oncolytic activity either alone or in combination with each other and using the murine CT26 colon carcinoma and 4T1 breast carcinoma models. We demonstrated that the admixture of these recombinant variants could promote the generation of the IL-15/IL-15Rα complex.

Oncolytic Efficacy of a Recombinant Vaccinia Virus Strain Expressing Bacterial Flagellin in Solid Tumor Models.

Oncolytic viral therapy is a promising novel approach to cancer treatment. Oncolytic viruses cause tumor regression through direct cytolysis on the one hand and recruiting and activating immune cells on the other. In this study, to enhance the antitumor efficacy of the thymidine kinase-deficient vaccinia virus (VV, Lister strain), recombinant variants encoding bacterial flagellin (subunit B) of (LIVP-FlaB-RFP), firefly luciferase (LIVP-Fluc-RFP) or red fluorescent protein (LIVP-RFP) were developed.

Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus.

Cancer cell lines responded differentially to type I interferon treatment in models of oncolytic therapy using vesicular stomatitis virus (VSV). Two opposite cases were considered in this study, glioblastoma DBTRG-05MG and osteosarcoma HOS cell lines exhibiting resistance and sensitivity to VSV after the treatment, respectively. Type I interferon responses were compared for these cell lines by integrative analysis of the transcriptome, proteome, and RNA editome to identify molecular factors determining differential effects observed.

The CIMP-high phenotype is associated with energy metabolism alterations in colon adenocarcinoma.

Background: CpG island methylator phenotype (CIMP) is found in 15-20% of malignant colorectal tumors and is characterized by strong CpG hypermethylation over the genome. The molecular mechanisms of this phenomenon are not still fully understood. The development of CIMP is followed by global gene expression alterations and metabolic changes.

Important molecular genetic markers of colorectal cancer.

Colorectal cancer (CRC) ranks third in the incidences of cancer morbidity and mortality worldwide. CRC is rather heterogeneous with regard to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers is used for molecular subtype determination, prognosis, and estimation of sensitivity to different drugs in practice.